The long term goal of this research, which falls in the area of organic synthesis known as biomimetic chemistry, is to construct compounds capable of acting as specific catalysts in a fashion comparable to that of enzymes. Such compounds, known as enzyme models, should possess a cavity that is complementary in shape and size to that of the substrate molecule and should possess functional groups properly arranged in space to allow interaction with the reaction site of the substrate molecule. A class of [1n]-metacyclophanes which we have named calixarenes(Gr., calix, chalice; arene, indicating the presence of aromatic rings in the macrocyclic array) have the potential for satisfying these criteria, and it is with the synthesis, characterization, and chemistry of these compounds that the present study is concerned. During the present grant period methods for synthesizing calixarenes containing four, six, and eight units and methods for introducing functional groups onto the aromatic rings have been developed. Also, we have found that the calix[4]arenes, which exist at room temperature as a pair of rapidly interconverting "cone" conformations, can be fixed in a single non-interconverting conformation (i.e. a "changeless calix") by conversion to ether derivatives and that either the "partial cone" or the "cone" conformation can be established depending on the derivatizing agent used. With this synthetic methodology now in hand, efforts are underway to synthesize a variety of appropriately functionalized calixarenes for testing as hydrolysis catalysts (chymotrypsin models), aldolization catalysts (aldolasemodels), farnesol phosphate cyclization catalysts, and oxygen carriers (heme models). Studies of calixarene catalysis in these systems might shed light on the mechanisms of enzymatic catalysis, will certainly establish patterns for the synthesis of better synthetic catalysts, and will give rise to many new compounds with novel structures which may have interesting properties and useful pharmacological activities.